Trattamento del tromboembolismo venoso con anticoagulanti tradizionali e di nuova generazione.

The paradigm of treatment of acute venous thromboembolism (VTE) has been recently challenged by the new direct oral anticoagulants (DOACs). The aim of the research project was to evaluate the impact of DOACs on the management of pulmonary embolism (PE), isolated distal deep vein thrombosis (IDDVT) and bleeding. The approval process of DOACs was delayed in Italy and did not include IDDVT and, until 2015, PE. Therefore, the projects underwent some changes, with the aim of building solid bases for subsequent studies that will adopt DOACs. The project on PE was focused on the prognostic stratification, by applying the Pulmonary Embolism Severity Index (PESI). The results of the study showed a 2 days significant difference of the median duration of hospital stay between low risk vs. high risk patients, as identified retrospectively by PESI. However, this difference has little clinical significance and led to hypothesize that prospectively adopting PESI may have a significant impact. With regards to IDDVT, a retrospective study was performed on 321 patients, who were treated with a short course of anticoagulation. The results showed a non negligible 15% rate of recurrent VTE events. Therefore, many cases of IDDVT should be considered in the context of major VTE and may benefit from an extended treatment. Finally, the management of anticoagulant-associated bleeding was explored in a literature review and includes general resuscitation, diagnosis and local treatment of the bleeding source, as well as transfusion of red cells, clotting factor replacements and administration of antidotes and other prohaemostatic agents. Reversal strategies for the ‘conventional’ anticoagulants are based on clinical evidence, whereas evidence on DOACs is emergin

Milvexian and other drugs targeting Factor XI: a new era of anticoagulation?

For almost 90 years, the discovery and development of anticoagulant drugs have focused on maximizing their antithrombotic efficacy while minimizing the risk of bleeding, in addition to providing manageable compounds with predictable and/or monitorable effects [...]

Trattamento del tromboembolismo venoso con anticoagulanti tradizionali e di nuova generazione.

The paradigm of treatment of acute venous thromboembolism (VTE) has been recently challenged by the new direct oral anticoagulants (DOACs). The aim of the research project was to evaluate the impact of DOACs on the management of pulmonary embolism (PE), isolated distal deep vein thrombosis (IDDVT) and bleeding. The approval process of DOACs was delayed in Italy and did not include IDDVT and, until 2015, PE. Therefore, the projects underwent some changes, with the aim of building solid bases for subsequent studies that will adopt DOACs. The project on PE was focused on the prognostic stratification, by applying the Pulmonary Embolism Severity Index (PESI). The results of the study showed a 2 days significant difference of the median duration of hospital stay between low risk vs. high risk patients, as identified retrospectively by PESI. However, this difference has little clinical significance and led to hypothesize that prospectively adopting PESI may have a significant impact. With regards to IDDVT, a retrospective study was performed on 321 patients, who were treated with a short course of anticoagulation. The results showed a non negligible 15% rate of recurrent VTE events. Therefore, many cases of IDDVT should be considered in the context of major VTE and may benefit from an extended treatment. Finally, the management of anticoagulant-associated bleeding was explored in a literature review and includes general resuscitation, diagnosis and local treatment of the bleeding source, as well as transfusion of red cells, clotting factor replacements and administration of antidotes and other prohaemostatic agents. Reversal strategies for the \u2018conventional\u2019 anticoagulants are based on clinical evidence, whereas evidence on DOACs is emergin

Antithrombotic treatment of retinal vein occlusion: a position statement from the Italian Society on Thrombosis and Haemostasis (SISET)

Retinal vein occlusion (RVO) represents a common cause of visual impairment and blindness. RVO may be associated with both local (e.g., hyperopia, glaucoma) and systemic (e.g., hypertension, diabetes, smoking, obesity, and dyslipidaemia) risk factors. The association with thrombophilia remains controversial. Data on the use of antithrombotic therapy for RVO are poor and inconsistent with most of the information being derived from observational studies. Here we provide a position statement from the Italian Society on Thrombosis and Haemostasis (SISET) to guide the clinical and therapeutic management of patients with RVO based on the available evidence and expert opinion

The Clinical Impact of the Pulmonary Embolism Severity Index on the Length of Hospital Stay of Patients with Pulmonary Embolism: A Randomized Controlled Trial.

BACKGROUND The Pulmonary Embolism Severity Index (PESI) is an extensively validated prognostic score, but impact analyses of the PESI on management strategies, outcomes and health care costs are lacking. Our aim was to assess whether the adoption of the PESI for patients admitted to an internal medicine ward has the potential to safely reduce the length of hospital stay (LOS). METHODS We carried out a multicenter randomized controlled trial, enrolling consecutive adult outpatients diagnosed with acute PE and admitted to an internal medicine ward. Within 48 h after diagnosis, the treating physicians were randomized, for every patient, to calculate and report the PESI in the clinical record form on top of the standard of care (experimental arm) or to continue routine clinical practice (standard of care). The ClinicalTrials.gov identifier is NCT03002467. RESULTS This study was prematurely stopped due to slow recruitment. A total of 118 patients were enrolled at six internal medicine units from 2016 to 2019. The treating physicians were randomized to the use of the PESI for 59 patients or to the standard of care for 59 patients. No difference in the median LOS was found between the experimental arm (8, IQR 6-12) and the standard-of-care arm (8, IQR 6-12) (p = 0.63). A pre-specified secondary analysis showed that the LOS was significantly shorter among the patients who were treated with DOACs (median of 8 days, IQR 5-11) compared to VKAs or heparin (median of 9 days, IQR 7-12) (p = 0.04). CONCLUSIONS The formal calculation of the PESI in the patients already admitted to internal medicine units did not impact the length of hospital stay

Archaeomagnetic and rock magnetic study of six kilns from North Africa (Tunisia and Morocco)

International audienceNew full-vector archaeomagnetic data for North Africa recovered from the study of six kilns, five from Tunisia and one from Morocco, are presented. Archaeological and historical considerations, along with three radiocarbon dates, indicate that the age of the kilns ranges between the 9th and 15th centuries AD. Rock magnetic analyses showed that the principal magnetic carriers are magnetite and low Ti titanomagnetite, along with variable contributions of thermally stable maghemite and a high coercivity phase with low unblocking temperatures. The magnetic mineralogy of the studied material is thermally stable and behaves ideally during archaeointensity experiments. Stepwise alternating field demagnetization isolated a single, stable, characteristic remanence component with very well defined directions at both specimen and structure levels. Mean archaeointensities have been obtained from successful classical Thellier experiments conducted on between five and eight independent samples per kiln. Thermoremanent magnetization (TRM) anisotropy and cooling rate effects upon TRM intensity have been investigated. The results showed that these effects are low for four of the six studied kilns, with differences between the uncorrected and corrected means of less than 3 per cent. For the other two structures differences between the uncorrected and corrected mean site intensities are 4.4 per cent and 5.8 per cent. These results highlight the necessity for TRM anisotropy and cooling rate corrections in archaeomagnetic studies if accurate archaeointensities are to be obtained. The new results suggest that high intensities occurred in Northwest Africa during the 9th century. Although more data are clearly needed to define this period of high intensity, the results are in agreement with the available European archaeointensity data. Acomparison between the newdata, other available archaeomagnetic determinations in nearby locations, and palaeosecular variation (PSV) curves derived from the regional SCHA.DIF.3k and global ARCH3K.1 geomagnetic field models shows good agreement between the new data and directional results derived from the models. However, some differences are observed between geomagnetic field models intensity results and available archaeointensity data for the studied regions. This highlights the need for new data for unexplored regions such as North Africa. The new data presented here better constrains the evolution of the geomagnetic field during historical times in this region. They represent a new step towards the construction of a reference PSV curve for Northwest Africa. Once established, this curve will represent a new dating method for this region

Rivaroxaban for the treatment of noncirrhotic splanchnic vein thrombosis: an interventional prospective cohort study.

Heparins and vitamin K antagonists are the mainstay of treatment of splanchnic vein thrombosis (SVT). Rivaroxaban is a potential alternative, but data to support its use are limited. We aimed to evaluate the safety and efficacy of rivaroxaban for the treatment of acute SVT. In an international, single-arm clinical trial, adult patients with a first episode of noncirrhotic, symptomatic, objectively diagnosed SVT received rivaroxaban 15 mg twice daily for 3 weeks, followed by 20 mg daily for an intended duration of 3 months. Patients with Budd-Chiari syndrome and those receiving full-dose anticoagulation for >7 days prior to enrollment were excluded. Primary outcome was major bleeding; secondary outcomes included death, recurrent SVT, and complete vein recanalization within 3 months. Patients were followed for a total of 6 months. A total of 103 patients were enrolled; 100 were eligible for the analysis. Mean age was 54.4 years; 64% were men. SVT risk factors included abdominal inflammation/infection (28%), solid cancer (9%), myeloproliferative neoplasms (9%), and hormonal therapy (9%); 43% of cases were unprovoked. JAK2 V617F mutation was detected in 26% of 50 tested patients. At 3 months, 2 patients (2.1%; 95% confidence interval, 0.6-7.2) had major bleeding events (both gastrointestinal). One (1.0%) patient died due to a non-SVT-related cause, 2 had recurrent SVT (2.1%). Complete recanalization was documented in 47.3% of patients. One additional major bleeding event and 1 recurrent SVT occurred at 6 months. Rivaroxaban appears as a potential alternative to standard anticoagulation for the treatment of SVT in non-cirrhotic patients. This trial was registered at www.clinicaltrials.gov as #NCT02627053 and at eudract.ema.europa.eu as #2014-005162-29-36

The Translation Factor eIF6 Is a Notch-Dependent Regulator of Cell Migration and Invasion

A growing body of evidence indicates that protein factors controlling translation play an important role in tumorigenesis. The protein known as eIF6 is a ribosome anti-association factor that has been implicated in translational initiation and in ribosome synthesis. Over-expression of eIF6 is observed in many natural tumours, and causes developmental and differentiation defects in certain animal models. Here we show that the transcription of the gene encoding eIF6 is modulated by the receptor Notch-1, a protein involved in embryonic development and cell differentiation, as well as in many neoplasms. Inhibition of Notch-1 signalling by γ-secretase inhibitors slowed down cell-cycle progression and reduced the amount of eIF6 in lymphoblastoid and ovarian cancer cell lines. Cultured ovarian cancer cell lines engineered to stably over-expressing eIF6 did not show significant changes in proliferation rate, but displayed an enhanced motility and invasive capacity. Inhibition of Notch-1 signalling in the cells over-expressing eIF6 was effective in slowing down the cell cycle, but did not reduce cell migration and invasion. On the whole, the results suggest that eIF6 is one of the downstream effectors of Notch-1 in the pathway that controls cell motility and invasiveness

Prediction Scores Do Not Correlate with Clinically Adjudicated Categories of Pulmonary Embolism in Critically Ill Patients

Copyright © 2014 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.BACKGROUND: Prediction scores for pretest probability of pulmonary embolism (PE) validated in outpatient settings are occasionally used in the intensive care unit (ICU).OBJECTIVE: To evaluate the correlation of Geneva and Wells scores with adjudicated categories of PE in ICU patients.METHODS: In a randomized trial of thromboprophylaxis, patients with suspected PE were adjudicated as possible, probable or definite PE. Data were then retrospectively abstracted for the Geneva Diagnostic PE score, Wells, Modified Wells and Simplified Wells Diagnostic scores. The chance-corrected agreement between adjudicated categories and each score was calculated. ANOVA was used to compare values across the three adjudicated PE categories.RESULTS: Among 70 patients with suspected PE, agreement was poor between adjudicated categories and Geneva pretest probabilities (kappa 0.01 [95% CI −0.0643 to 0.0941]) or Wells pretest probabilities (kappa −0.03 [95% CI −0.1462 to 0.0914]). Among four possible, 16 probable and 50 definite PEs, there were no significant differences in Geneva scores (possible = 4.0, probable = 4.7, definite = 4.5; P=0.90), Wells scores (possible = 2.8, probable = 4.9, definite = 4.1; P=0.37), Modified Wells (possible = 2.0, probable = 3.4, definite = 2.9; P=0.34) or Simplified Wells (possible = 1.8, probable = 2.8, definite = 2.4; P=0.30).CONCLUSIONS: Pretest probability scores developed outside the ICU do not correlate with adjudicated PE categories in critically ill patients. Research is needed to develop prediction scores for this population

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p < .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p < .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come